Synthesis, biological evaluation and molecular docking study of pyrimidine linked thiazolidinedione derivatives as potential antimicrobial and antitubercular agents.

The design and development of novel antimicrobial agents are highly desired to combat the emergence of medication resistance against microorganisms that cause infections. A series of new pyrimidine-linked thiazolidinedione derivatives (5a-j) were synthesized, characterized, and their antimicrobial properties assessed in the current investigation. Here, novel pyrimidine-linked thiazolidinedione compounds were designed using the molecular hybridization approach. Elemental and spectral techniques were used to determine the structures of the synthesized hybrids. The majority of compounds showed encouraging antibacterial properties. Among the active compounds, 5g, 5i, and 5j showed 1.85, 1.15, and 1.38 times the activity of streptomycin against S. aureus, respectively, with MIC values of 6.4, 10.3, and 8.6 µM. With MIC values of 10.8, 21.9, and 15.4 µM, respectively, the compounds 5g, 5i, and 5j showed 2.14, 1.05, and 1.50 times the activity of linezolid against the methicillin-resistant S. aureus (MRSA) strain. Furthermore, when compared to the reference medications, compounds 5g, 5i, and 5j demonstrated broad-range antimicrobial efficacy against all tested strains of bacteria and fungus. Out of all the compounds that were investigated, compounds 5g, 5i, and 5j showed noteworthy anti-tubercular activity. 5g is the most effective, 1.59 times more effective than reference drug isoniazid. To anticipate the binding manner, the synthesized potent compounds were subjected to molecular docking into the active binding site of MRSA and the mycobacterial membrane protein large 3 (MmpL3) protein. The compounds 5g, 5i, and 5j may eventually serve as lead compounds in the search for antimicrobial and anti-TB therapeutic agents.

Synthesis, antitubercular profile and molecular docking studies of quinazolinone-based pyridine derivatives against drug-resistant tuberculosis.

The promising quinazolinone-based pyridine derivatives (4a-j) were synthesized and subsequently tested for their antimycobacterial activities against the various drug-sensitive and drug-resistant Mycobacterium tuberculosis (Mtb) strains to combat infectious diseases and address growing concerns about the devastating effects of tuberculosis (TB). Utilizing 1H NMR, 13C NMR, and mass spectra, the structural and molecular confirmation of the synthesized compounds were deciphered. With minimum inhibitory concentration (MIC) values ranging from 0.31 to 19.13 µM, the results showed that compounds 4e and 4f showed promise anti-TB action against both drug-sensitive and drug-resistant TB strains. To study the cytotoxicity of synthesized molecules, normal Vero and mouse macrophage (RAW264.7) cell lines were utilized. Remarkably, it was revealed that at the highest concentration tested, none of the newly synthesized molecules were toxic to the Vero cell line. The binding patterns of the potent compounds 4b, 4e and 4f in the active site of the mycobacterial membrane protein Large 3 (MmpL3) protein are also revealed by molecular docking studies, which has contributed to the development of a structural rationale for Mtb inhibition. The physicochemical characteristics of the compounds were then predicted using theoretical calculations. Overall, the molecular docking results, physiochemical properties, and observed antimycobacterial activity all point to compound 4e with trifluoromethyl and compound 4f with nitro moiety as potential quinazolinone linked pyridine-based MmpL3 inhibitors.Communicated by Ramaswamy H. Sarma.

Ultrasound assisted fabrication of InVO4/In2S3 heterostructure for enhanced sonophotocatalytic degradation of pesticides.

A cost effective and environmentally benign ultrasonic method has been developed for the synthesis of InVO4 (InV), In2S3 (InS) and the InVO4/In2S3 heterostructure (InV/InS). All the designed materials were evaluated for their structural, morphological, spectroscopic, and electrochemical characterizations. Materials were examined for photocatalytic, sonocatalytic, and sonophotocatalytic degradation of carbofuran (CBF) and diazinon (DZN) pesticides under visible light. InV/InS showed enhanced degradation of CBF and DZN when compared to InV and InS. Photocatalytic degradation was accelerated by ultrasonication and found to degrade 97 and 98 % of CBF and DZN in 60 and 70 min, respectively. The reaction conditions, like pH, catalyst dosage, acoustic intensity, and ultrasound power, were carefully optimized. Electron spin resonance (ESR) spectroscopy shows the generation of superoxide radical anion and hydroxyl radicals as reactive species during photoredox reaction. The CBF and DZN degradation intermediates were analyzed using liquid chromatography mass spectroscopy (LC-MS) that shows the mineralization of the CBF and DZN to CO2 and H2O. The effect of Cl-, and PO43- were examined towards degradation of CBF and DZN under optimal conditions in the presence of InV/InS. The degradation of CBF and DZN is decreased in presence of Cl-, CO32- and NO3- but PO43- ions does not show any effect on degradation. The bandgap and Mott-Schottky results suggest the existence of type-II heterostructure between InV and InS through the interface. The synthesis of heterostructure and degradation of pesticides utilizes ultrasonic waves, which prove their multiple applications and attract researchers towards the effective use of sonication.

Theoretical and experimental investigation of novel quinazoline derivatives: synthesis, photophysical, reactive properties, molecular docking and selective HSA biointeraction.

Two new quinazoline derivatives (2a and 2b) were successfully synthesized in this work using the condensation technique in excellent yields. Using spectroscopic techniques and elemental analyses, the compounds were completely characterized. Density functional theory (DFT) computations have been used to examine the title compound's reactive characteristics. Chemical reactivity was predicted using local reactive descriptors and molecule electrostatic potential. Additionally, Time dependent DFT (TD-DFT) simulations were used to examine the impact of solvents on the photophysical characteristics. The affinity of compounds 2a and 2b for human serum albumin (HSA) was further explored using several electronic spectroscopies. Through static mechanisms, both compounds reduce the intrinsic fluorescence of HSA. It is determined that the HSA-2b complex's binding constant is significantly greater than the HSA-2a complex. The fluorescence spectrum measurements proved that the HSA underwent structural changes after interaction with these compounds. It was demonstrated by site marker competitive displacement studies that compounds 2a and 2b preferred to bind to site I in HSA subdomain IIA. Additionally, synchronised fluorescence spectra were utilized to analyze how HSA's conformation changed after interacting with various substances. The molecular docking investigations of these compounds with the three critical HSA binding sites, comprising subdomains IIA, IIIA, and IB, further confirmed the experimental findings. The significant contact between the investigated compounds and HSA was supported by the docking simulations.Communicated by Ramaswamy H. Sarma.

A sonochemical synthesis of SrTiO3 supported N-doped graphene oxide as a highly efficient electrocatalyst for electrochemical reduction of a chemotherapeutic drug.

A sonochemical based green synthesis method playa powerful role in nanomaterials and composite development. In this work, we developed a perovskite type of strontium titanate via sonochemical process. SrTiO3 particles were incorporated with nitrogen doped graphene oxide through simple ultrasonic irradiation method. The SrTiO3/NGO was characterized by various analytical methods. The nanocomposite of SrTiO3/NGO was modified with laser-induced graphene electrode (LIGE). The SrTiO3/NGO/LIGE was applied for electrochemical sensor towards chemotherapeutic drug detection (nilutamide). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to examine the electrochemical performance of nilutamide (anti-cancer drug). DPV was found to be more sensitive and found to exhibit a sensitivity 8.627 µA µM-1 cm-2 for SrTiO3/NGO/LIGE with a wide linear range (0.02-892 µM) and low Limit of detection (LOD: 1.16 µM). SrTiO3/NGO/LIGE has been examined for the detection of nilutamide in blood serum and urine samples and obtained a good recovery in the range of 97.2-99.72 %. The enhanced stability and selectivity and practical application results indicates the suitability of SrTiO3/NGO/LIGE towards the detection of nilutamide drug in pharmaceutical industries.

Sonochemical construction of hierarchical strontium doped lanthanum trisulfide electrocatalyst: An efficient electrode for highly sensitive detection of ecological pollutant in food and water.

Herbicides are used constantly in agriculture to enhance productivity across the globe. This herbicide monitoring requires utmost importance since its high dose leads to ecological imbalance and a negative impact on the environment. Moreover, a quantification of toxic herbicide is one of the important problems in the food analysis. In this work, deals with the development of a simple, and facile one-pot sonochemical synthesis of strontium doped La2S3 (Sr@La2S3). Morphological and structural characterization confirms the doping of Sr@La2S3 to generate a hierarchical layered structure. The electrochemical performance of modified with rotating disk electrode (RDE) using Sr@La2S3 composite is high, compared to La2S3 and bare electrodes towards the quantitative detection of mesotrione (MTO) in phosphate buffer. Sr@La2S3/RDE showed good sensitivity for MTO detection and it exhibit a range of 0.01-307.01 µM and limit of detection of 2.4 nM. Besides, the selectivity of fabricated electrode is high as it can electrochemically reduce MTO particularly, even in the presence of other chemicals, biological molecules and inorganic ions. The repeatability of MTO detection is high even after 30 days with a lower RSD values. Hence, simple fabrication of Sr@La2S3/RDE could be a novel electrode for the sensitive, selective, and reproducible determination of herbicides in real-time applications.

Design, synthesis, molecular docking and pharmacological evaluation of novel triazine-based triazole derivatives as potential anticonvulsant agents.

Triazine-linked triazole compounds (4a-j) were designed, synthesized, and then examined for their anticonvulsant abilities. Compounds 4e, 4f, 4g, 4i, and 4j displayed significant anticonvulsant activity in both maximum electroshock seizure (MES) and pentylenetetrazole (PTZ) induced seizure during the preliminary screening. The phase II anticonvulsant activity statistics revealed that compounds 4e, 4f, 4g, 4i, and 4j demonstrated excellent activity as compared to the conventional drugs methaqualone and valproate, supporting the potential of these triazine-linked triazole analogues as novel anticonvulsant agents. To take use of the findings, computational parameters including docking analysis and drug-likeness prediction were carried out. Molecular modelling studies supported the essential pharmacophoric information that the structure activity relationship offered. The triazine-linked triazole analogues that were investigated might be viewed as helpful models for future research and derivatization.

Design, synthesis and molecular docking studies of imidazole and benzimidazole linked ethionamide derivatives as inhibitors of InhA and antituberculosis agents.

To explore effective antituberculosis agents, a new class of imidazoles and benzimidazoles linked ethionamide analogs were designed and synthesized. The elemental analysis, 1H NMR, 13C NMR and mass spectral data were used to characterize all of the novel analogs. In vitro activity against Mycobacterium tuberculosis (Mtb) H37Rv was assessed for all of the target compounds. The hydroxy and nitrile moieties on the imidazole ring, as well as the hydroxy and methoxy groups on the benzimidazole ring connected to the ethionamide side chain, were shown to be advantageous. In our cell viability experiment against the Vero cell line, all of the compounds were non-cytotoxic even at 100 µM. To confirm the powerful analogs target identification, we investigated their in vitro inhibitory action on an M. tuberculosis InhA over-expressing (Mtb InhA-OE) strain, which yielded MICs nearly twice those of the Mtb H37Rv strain. Furthermore, the results of molecular docking confirmed the experimental findings. Additionally, the molecules were evaluated in silico for ADMET and drug similarity features. The experimental observation enables the newly generated ethionamide derivatives to be attractive candidates for the creation of newer and better anti-TB agents.

Gadolinium sesquisulfide anchored N-doped reduced graphene oxide for sensitive detection and degradation of carbendazim.

Agriculture is having a major role in solving issues associated with food shortages across the globe. Carbendazim (CZM) is one of the fungicides which is commonly used in agriculture to grow crops in large quantities and fast. Monitoring CZM content is in high demand for environmental remediation. The present work deals with the synthesis of gadolinium sesquisulfide anchored Nitrogen-doped reduced graphene oxide (Gd2S3/NRGO) through a simple microwave-assisted method. X-ray diffraction and morphological studies confirm the formation of the nanocomposite. Gd2S3/NRGO showed enhanced activity both in electrochemical detection and light-driven degradation of CZM compared to Gd2S3 and NRGO. Gd2S3/NRGO modified glassy carbon electrode (GCE) exhibit a wide linear range of 0.01-450 µM CZM with 0.009 µM LOD using differential pulse voltammetry (DPV). Gd2S3/NRGO@GCE showed good selectivity, stability, and recovery (98.13-99.10%) in the river water sample. In addition, Gd2S3/NRGO has been explored towards the visible-light-induced degradation of CZM. The reactions conditions were optimized to achieve maximum efficiency. 94% of CZM was degraded within 90 min in presence of Gd2S3/NRGO. Mechanism of electrochemical redox reaction and degradation of CZM in presence of Gd2S3/NRGO has been explored to the maximum extent possible. Degradation intermediates were identified using LC-MS.

Click synthesis of 1,2,3-triazole based imidazoles: Antitubercular evaluation, molecular docking and HSA binding studies.

Using Cu(I)-catalyzed cycloaddition of alkyne and azide reaction (CuAAC), a series of novel 1,2,3-triazole based imidazole derivatives (3a-e) have been synthesized. The synthesized molecules were characterized by spectroscopic techniques such as 1H NMR, 13C NMR, mass and elemental analysis. Antitubercular activity (anti-TB) against Mycobacterium tuberculosis H37Rv (Mtb) and cytotoxic activity against the mammalian Vero cell line was screened for the synthesized compounds. The compounds 3d and 3e displayed potent in vitro antitubercular activity and may serve as a lead for further optimization. Besides, the experimental findings were in line with the results of molecular docking. Also, the synthesized compounds have also been analyzed for ADME properties and the experimental finding facilitates the development of new and more potent anti-TB agents in this series in the future. Using fluorescence and UV-vis absorption spectroscopy, the binding interaction of compounds (3d and 3e) with human serum albumin (HSA) was investigated. The results showed that, as a result of HSA-compound complex, the fluorescence quenching of HSA by test compounds was a static quenching process. According to Forster's theory, energy transfer efficiency is calculated.